Interactions between the renin-angiotensin system and dyslipidemia: relevance in atherogenesis and therapy of coronary heart disease.

ABSTRACT

Hypertension and hypercholesterolemia, two major risk factors for atherosclerotic disease, frequently coexist in patients with hypertension and CAD. Data from clinical studies suggest the existence of lipoprotein-neurohormonal interactions that may adversely affect vascular structure and reactivity. Data from preclinical studies suggest that RAS may be upregulated by abnormal lipids, most likely via production of ox-LDL. On the other hand, activation of RAS leads to release of ROS and transcriptional upregulation of LDL and ox-LDL uptake in macrophages, smooth muscle cells and endothelial cells. These findings extend our understanding of the interplay among risk factors to synergistically increase cardiovascular risk, and of the anti-atherosclerotic effects of local ACE inhibition to reduce cardiovascular risk. Trials aimed at modifying RAS along with drugs lowering total- and LDL-cholesterol levels and inhibitors of oxidative modification of LDL-cholesterol will address the clinical relevance of this biological interaction.